Abstract
According to results from a phase II study, abemaciclib shows single-agent activity in women with metastatic HER2-negative, ER-positive breast cancer whose disease has progressed on endocrine therapy and chemotherapy. The objective response rate to this investigational CDK4/6 inhibitor was 19.7%, with 28.2% of responses lasting at least a year.
Results from a phase II study indicate that abemaciclib (Eli Lilly), an investigational CDK4/6 inhibitor, demonstrates single-agent activity in women with advanced HER2-negative, ER-positive breast cancer whose disease has progressed on endocrine therapy and chemotherapy. The data were presented by Maura Dickler, MD, of the breast medicine service at Memorial Sloan Kettering Cancer Center in New York, NY, during the American Society of Clinical Oncology's annual meeting in Chicago, IL, June 3–7.
Cell-cycle control is frequently disrupted in ER-positive breast cancer, Dickler said, “making key regulators such as CDK4 and CDK6 rational targets for inhibition” with drugs like abemaciclib, which halts the cell cycle at the G1 phase.
A total of 132 patients with advanced metastatic breast cancer were enrolled on the MONARCH1 study. The objective response rate to abemaciclib was 19.7%, with a median duration of 8.6 months and 28.2% of responses lasting at least 12 months. The median progression-free survival was 6 months, and the median overall survival was 17.7 months.
Abemaciclib was largely well tolerated, especially considering the patient population, Dickler reported: Only 7.6% discontinued treatment due to toxicity, and diarrhea, a main side effect, was quickly resolved. Neutropenia was less commonly seen than with other therapies in this class, “probably because of the drug's differential impact on CDK6 inhibition,” she said, noting that abemaciclib is 14 times more potent against CDK4 than CDK6.
To date, palbociclib (Ibrance; Pfizer) is the sole CDK4/6 inhibitor to have gained the FDA's conditional approval as first-line therapy, in combination with letrozole, for postmenopausal women with locally advanced or metastatic HER2-negative, ER-positive breast cancer. Ribociclib (Novartis) is in phase III development; meanwhile, abemaciclib was designated as a Breakthrough Therapy by the FDA in October 2015.
In a study of patients with heavily pretreated, advanced metastatic breast cancer, “any responses we see, we can fairly well assume to be a consequence of the drug,” said Tatiana Prowell, MD, breast cancer scientific liaison with the FDA's Office of Hematology and Oncology Products. “That's why most successful Breakthrough Therapy requests, including the one for abemaciclib, have relied on objective and/or durable responses, because both are readily interpretable end points in single-arm trials, especially in a refractory patient population.”
These scans of a previously treated patient with advanced breast cancer and extensive liver metastases show tumor regression after two cycles of treatment with abemaciclib. (Originally published in Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Cancer Discov 2016;6:740–53.)
These scans of a previously treated patient with advanced breast cancer and extensive liver metastases show tumor regression after two cycles of treatment with abemaciclib. (Originally published in Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Cancer Discov 2016;6:740–53.)
Abemaciclib is also undergoing two phase III assessments in breast cancer—in combination with fulvestrant (Faslodex; AstraZeneca) or with a nonsteroidal aromatase inhibitor. Because it appears to cross the blood–brain barrier, abemaciclib might be effective in patients with central nervous system metastases, Dickler added. A phase II evaluation is under way in patients with breast cancer, non–small cell lung cancer, or melanoma that has spread to the brain. –Alissa Poh
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